Oxidative stress plays a key role in the pathophysiology of chronic kidney disease (CKD). Most studies have investigated peripheral redox state focus on plasma, but not in different immune cells. Our study analyzed several redox state markers in plasma and isolated peripheral polymorphonuclear (PMNs) and mononuclear (MNs) leukocytes from advanced-CKD patients, also evaluating differences of hemodialysis (HD) and peritoneal dialysis (PD) procedures. Antioxidant (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH)) and oxidant parameters (xanthine oxidase (XO), oxidized glutathione (GSSG), malondialdehyde (MDA)) were assessed in plasma, PMNs and MNs from non-dialysis-dependent-CKD (NDD-CKD), HD and PD patients and healthy controls. Increased oxidative stress and damage were observed in plasma, PMNs and MNs from NDD-CKD, HD and PD patients (increased XO, GSSG and MDA; decreased SOD, CAT, GPX and GSH; altered GSSG/GSH balance). Several oxidative alterations were more exacerbated in PMNs, whereas others were only observed in MNs. Dialysis procedures had a positive effect on preserving the GSSG/GSH balance in PMNs. Interestingly, PD patients showed greater oxidative stress than HD patients, especially in MNs. The assessment of redox state parameters in PMNs and MNs could have potential use as biomarkers of the CKD progression.

Kidney transplantation is the best option for patients with end-stage renal disease. Despite the improvement in cardiovascular burden (leading cause of mortality among patients with chronic kidney disease), cardiovascular adverse outcomes related to the inflammatory process remain a problem. Thus, the aim of the present study was to characterize the immune profile and microvesicles of patients who underwent transplantation. We investigated the lymphocyte phenotype (CD3, CD4, CD8, CD19, and CD56) and monocyte phenotype (CD14, CD16, CD86, and CD54) in peripheral blood, and endothelium-derived microvesicles (annexin V+CD31+CD41–) in plasma of patients with advanced chronic kidney disease (n = 40), patients with transplantation (n = 40), and healthy subjects (n = 18) recruited from the University Hospital “12 de Octubre” (Madrid, Spain). Patients with kidney transplantation had B-cell lymphopenia, an impairment in co-stimulatory (CD86) and adhesion (CD54) molecules in monocytes, and a reduction in endothelium-derived microvesicles in plasma. The correlations between those parameters explained the modifications in the expression of co-stimulatory and adhesion molecules in monocytes caused by changes in lymphocyte populations, as well as the increase in the levels of endothelial-derived microvesicles in plasma caused by changes in lymphocyte and monocytes populations. Immunosuppressive treatment could directly or indirectly induce those changes. Nevertheless, the particular characteristics of these cells may partly explain the persistence of cardiovascular and renal alterations in patients who underwent transplantation, along with the decrease in arteriosclerotic events compared with advanced chronic kidney disease. In conclusion, the expression of adhesion molecules by monocytes and endothelial-derived microvesicles is related to lymphocyte alterations in patients with kidney transplantation.

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Synthesis of Homochiral Cyclopentane Derivatives by BeckmannFragmentation of 1-Substituted 2-Norbornanones.-The method is found to work well, since the reactions can be carried out under mild conditions and Beckmann rearrangement can be avoided even in the presence of iodide substituents.-(GARCIA MARTINEZ, A.; TESO VILAR, E.; GARCIA FRAILE, A.; DE LA MOYA CERERO, S.; DIAZ OLIVA, C.; SUBRAMANIAN, L. R.; MAICHLE, C.; Tetrahedron: Asymmetry 5 (1994) 5, 949-954; Dep. Quim. Org.,

Background and Aims Epigenetic signals play a principal role in homeostasis, but also may promote diseases including cardiovascular diseases (CVDs) when are altered. Extracellular vesicles (EVs) or plasma circulating DNA and RNA may have relevant functions in both physiological and pathophysiological contexts related to the epigenetic intercellular communication. Thus, changes in the endothelial or platelet EVs, or the plasma circulating methylated DNA may contribute to the chronic inflammation and the subsequent CVDs in chronic kidney disease patients, particularly when are in hemodialysis (HD). Dialysis membranes do not usually allow the passage of molecules larger than 30-40 kDa. However, the new system of expanded hemodialysis (HDx) with a medium-cut-off membrane (MCO), due to its characteristics, could alter the plasma content of these EVs and DNA methylation, and thereby, promote the development of CVDs. Therefore, our study evaluates whether global plasma DNA methylation and EVs content are modified during an HDx session. Method For this study, we selected 12 dialysis patients: HDx patients (n=6; dialyzed with MCO) and control group (n=6; dialyzed with other HD membranes). Before and after a dialysis session, plasma samples were obtained. EVs were isolated by ultracentrifugation, and the total number of EVs and platelet and endothelial-derived EVs were characterized and quantified by flow cytometry. RNA and DNA extraction and quantification were carried out using different kits and NanoDrop spectrophotometer. DNA methylation was assessed with a 5-methyl cytosine (5-mC) DNA assay kit. Results As shown in the figure, after a dialysis session with the HDx, no significant differences were observed in the total number of EVs, as well in the number of platelet- and endothelial-derived EVs, in comparison to those observed in HDx patients before the dialysis session. By contrast, patients dialyzed with other HD membranes presented differences in the number of total EVs and platelet and endothelial EVs, which decreased significantly (p<0.05) after the dialysis session. Concerning DNA methylation, no statistically significant changes in total DNA 5-mC (%) were observed in both HDx and control patients after the dialysis session. However, a slight tendency to decrease methylated DNA was observed with the HDx compared to other HD membranes (control). Moreover, no significant changes in DNA and RNA % were observed after dialysis session in both HDx and control group. Conclusion To our knowledge, this is the first study to investigate the influence of the HDx technique on the content of plasma cellular EVs and DNA methylation status. HDx does not affect EVs levels, although it shows a tendency to purify plasma methylated DNA. Although this study was not designed to analyze the comparative effectiveness between different membranes, interestingly this effect in epigenetic signals was not observed with other HD membranes, where patients showed a marked reduction of EVs content. The differential activity of HDx about other HD membranes deserves further investigation. Funding (PI17/01029; PI19/00240; ISCIII-FEDER). Santander/UCM PR41/17-20964. Spanish Society of Nephrology 2018. UAH-GP2018-4